CC BY
1812. Mc. Closkey E.V., Harvey N.C., Johansson H., Kanis J.A. FRAX updates 2016 // Curr. Opin.Rheumatol. — 2016. — 28(4). — P. 433-441.
Работа поступила в редакцию 27.01.2019 года. Рекомендована к печати на заседании редакционной коллегии после рецензирования
УДК 616.36-003.826:616.61-002.3]-036-071:613.25 DOI http://dx.doi.org/10.5281/zenodo.2639500
O. S. Khukhlina, A. A. Antoniv
THE CLINICAL FEATURES OF THE NON-ALCOHOLIC FATTY LIVER DISEASE WITH CHRONIC KIDNEY DISEASE (CHRONIC PYELONEPHRITIS) AND OBESITY
Higher educational institution «Bukovinian State Medical University», Chernivtsi, Ukraine
e-mail: antonivalona@ukr. net
Summary. Khukhlina O. S., Antoniv A. A. THE CLINICAL FEATURES OF THE NON-ALCOHOLIC FATTY LIVER DISEASE WITH CHRONIC KIDNEY DISEASE (CHRONIC PYELONEPHRITIS) AND OBESITY. Urgency of the chronic kidney disease (CKD) with nonalcoholic fatty liver disease (NAFLD) comorbidity in obese patients' problem is a significant increase in the frequency of this type of comorbidity (15-30%).The objective: to find out the clinical features of the non-alcoholic fatty liver disease with chronic kidney disease (chronic pyelonephritis) comorbidity course in obese subjects, depending on the form of NAFLD and the stage of CKD. The object and methods of research. 384 patients with NAFLD were examined: 84 of them with NAFLD with comorbid obesity I degree (group 1), which contained 2 subgroups: 32 patients with non-alcoholic steatosis (NAS) and 52 patients with non-alcoholic steatohepatitis (NASH); 270 patients with NAFLD with comorbid obesity of the I degree and CKD I-III stage (group 2), including 110 patients with NAS and 160 patients with NASH. The control group consisted of 90 patients with CKD of the I-III stage with normal body weight (group 3). The average age of patients was (45.8 ± 3.81) years. Results. Patients with NAS with comorbidity of obesity and CKD have a significantly higher incidence of manifestation of clinical syndromes compared with those in the group of patients with NAS and obesity without CKD. Clinical and biochemical cholestatic syndrome was established in a large proportion of patients with NASH in both groups. Clinical manifestations of cholestasis syndrome in patients with the comorbidity with CKD occurred in 1.9 times more often (p <0,05) compared with the course of NAS without CKD, also biochemical markers of cholestatic syndrome were registered even more often - 2.1 times (p <0.05). Conclusion. Clinical course of nonalcoholic steatosis and steatohepatitis with the comorbidity with obesity and CKD is characterized by higher frequency and intensity of clinical syndromes.
Key words: nonalcoholic fatty liver disease, obesity, chronic kidney disease.
Реферат. Хухлина О. С., Антонов А. А. КЛИНИЧЕСКИЕ ОСОБЕННОСТИ НЕАЛКОГОЛЬНОЙ ЖИРОВОЙ БОЛЕЗНИ ПЕЧЕНИ И ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК (ХРОНИЧЕСКИЙ ПИЛОНЕФРИТ) И ОЖИРЕНИЯ. В статье приведено теоретическое обобщение клинического исследования особенностей течения неалкогольной жировой болезни печени у больных ожирением в зависимости от формы неалкогольной жировой болезни печени и стадии хронической болезни почек, характеризующиеся высокой
© Khukhlina O. S., Antoniv A. A.
частотой и интенсивностью клинических синдромов, манифестация которых достоверно возрастает в условиях присоединения данных патологий.
Ключевые слова: неалкогольная жировая болезнь печени, ожирение, хроническая болезнь почек.
Реферат. Хухлша О. С., Антотв А. А. КЛ1Н1ЧН1 ОСОБЛИВОСТ1 ХРОН1ЧНО1 ШЕАЛКОГОЛЬШО1 ХВОРОБИ ПЕЧЕНК1 ТА ХРОШ1ЧШО1 ХВОРОБИ НИРОК (ХРОН1ЧНИЙ ШЕЛОШЕФРИТ) I ОЖИР1ШШЯ. У статтi наведено теоретичне узагальнення клiнiчного дослвдження особливостей переб^ неалкогольний жирово! хвороби печшки у хворих нa ожирiння залежно ввд форми неалкогольно! жирово! хвороби печшки та стади хротчно! хвороби нирок, що характеризуеться високою частотою i iнтенсивнiстю клiнiчних синдромiв, машфестащя яких достовiрно зростае в умовах приеднання даних патологiй.
Ключовi слова: неалкогольнажирова хвороба печiнки, ожирiння, хрошчна хвороба
нирок.
Actuality of the chronic kidney disease (CKD) with nonalcoholic fatty liver disease (NAFLD) comorbidity in obese patients' problem is a significant increase in the frequency of this type of comorbidity (15-30%) [1, 2, 3, 4, 5]. CKD affects up to 8% of the world adult population, and its prevalence increases significantly in the elderly population (up to 38%), which suffers from diseases such as obesity, metabolic syndrome, diabetes, arterial hypertension and smoking.
The objective: to find out the clinical features of the non-alcoholic fatty liver disease with chronic kidney disease (chronic pyelonephritis) comorbidity course in obesity patients, depending on the form of non-alcoholic fatty liver disease and the stage of chronic kidney disease. The object and methods of research. 384 patients with NAFLD were examined: 84 of them with NAFLD with comorbid obesity I degree (group 1), which contained 2 subgroups: 32 patients with non-alcoholic steatosis (NAS) and 52 patients with non-alcoholic steatohepatitis (NASH); 270 patients with NAFLD with comorbid obesity of the I degree and CKD I-III stage (group 2), including 110 patients with NAS and 160 patients with NASH. The control group consisted of 90 patients with CKD of the I-III stage with normal body weight (group 3). The average age of patients was (45.8 ± 3.81) years.
The diagnosis of NASH was made according to a unified clinical protocol approved by the MoH of Ukraine Order No. 826 dated November 6, 2014, in the presence of criteria for the exclusion of chronic diffuse liver disease of viral, hereditary, autoimmune or medicinal origin as a cause of cholestatic or cytolytic syndromes, as well as the results of the USG examination. Diagnosis and treatment of CKD was conducted in accordance with the clinical guidelines of the SI "Institute of Nephrology of NAMS of Ukraine" (2012). The study involved patients with CKD of the I-III stage without nephrotic syndrome with chronic uncomplicated pyelonephritis in the phase of exacerbation subsiding or with a latent course. The statistical analysis of the results was carried out in accordance with the type of research and the types of numerical data that were obtained. Distribution normality was verified using the Lilliefors and Shapiro-Wilk tests and by the direct visual evaluation of eigenvalues distribution histograms. Quantitative indices having a normal distribution are represented as mean (M) ± standard error (S). In the nonparametric distribution the data are presented as median (Me) as a measure of position, upper (Q75) and lower (Q25) quartiles as a measure of dispersion. Discrete indices are presented in the form of absolute and relative frequencies (percentage of observations to the total number of examined). Parametric tests with the assessment of Student's t-test, Fisher's F-test were used to compare the data that had normal distribution. The median test, Mann-Whitney Rank U-test, and Wilcoxon signed-rank test for multiple comparisons (in the case of dependent groups) were used in abnormal distribution. The Pearson correlation analysis was used to estimate the degree of dependence between variables in parametric distribution and the Spearman rank correlation coefficient was used in the case of the indices distribution that significantly differed from the normal one. In order to compare discrete values in independent groups, the criterion x2 of maximum probability (log-likelihood) (MP x2) was used; to compare the pairs of discrete values, the calculation of the modification of the exact criterion by Fisher (mid-p) was used. Determination of the diagnostic advantage of the method was performed on the basis of assessing the quality of diagnostic procedures using ROC-analysis, with
the determination of sensitivity, specificity, diagnostic value, area under the ROC-curve (AUROC), diagnostic odds ratio (DOR). Statistica for Windows version 8.0 (Stat Soft Inc., USA), Microsoft Excel 2007 (Microsoft, USA) software packages were used for statistical and graphical analysis of the obtained results.
Results of the research and their discussion. According to the data obtained, patients with NAS with comorbidity of obesity and CKD have a significantly higher incidence of manifestation of clinical syndromes compared with those in the group of patients with NAS and obesity without CKD (Table 1). Thus, the incidence of astheno-vegetative syndrome was 1.7 times more frequent (p <0.05), dyspeptic manifestations - more often in 1.8 times (p <0.05), hepatomegaly - more often in 1.4 times (p < 0.05), splenomegaly - respectively 3.8 times (p <0,05). Clinical manifestations of cholestasis syndrome in patients with the comorbidity with CKD occurred in 1.9 times more often (p <0,05) compared with the course of NAS without CKD, also biochemical markers of cholestatic syndrome were registered even more often - 2.1 times (p <0.05) (Table 1). Initial manifestations of hepatic-cellular deficiency (blood fibrinogen content, prothrombin time and index) in patients with NAS with the comorbidity with CKD were determined 5.3 times more often (p <0.05) than in the course of NAS without CKD.
Table 1.
Frequency of clinical syndromes manifestation of nonalcoholic liver steatosis depending on the presence of comorbid pathology: obesity and CKD, (n,%)
Syndromes Groups of examined patients
NAS, obesity, CKD, n=110 NAS, obesity, n=32
Absolute data % Absolute data %
Astheno -vegetative 78 70,9 13 40,6*
Dyspeptic 37 33,6 6 18,8*
Cholestatic (clinical) 34 30,9 5 15,6*
Hepatomegaly 107 97,3 23 71,8*
Splenomegaly 13 11,8 1 3,1*
Cholestasis (biochemical) 43 39,1 6 18,8*
Hepatic-cellular insufficiency 8 26,7 1 5,0*
Impairment of glucose tolerance 97 88,2 21 65,6*
Note: * - the difference is statistically significant in comparison with the indicator in the group of patients with NAS, CKD and obesity (p <0.05)
In the analysis of clinical manifestations of NASH patients with obesity and CKD, it should be noted that their frequency and intensity are significantly higher in comparison with the group of patients with NASH without pathology of the kidneys (Table 2). In particular, the symptoms of astheno-vegetative syndrome were observed more often: 1.6 times (p <0.05), as compared to patients in group 1, which was probably due to increased accumulation of non-damaged liver metabolic products under the condition of an accompanying CKD in the phase of exacerbation.
Manifestations of dyspepsia in patients in group 2 also occurred more often than in patients in group 1 (1,3 times, p <0,05), indicating a violation of digestive processes due to the production of an inadequate bile, possible accompanying colon dysbiosis due to repeated courses of CKD antibacterial therapy and uroseptics.
A feeling of heaviness or moderate pain in palpation in the right hypochondrium was recorded in patients in group 2 with a frequency exceeding that in patients in group 1: 2.6 times (p <0.05), which was probably due to stretching Glisson's liver capsule due to hepatomegaly, with accompanying dysfunction of the sphincter apparatus of the bile ducts, which are often observed in obese patients, as well as with CKD in the phase of exacerbation.
Table 2
Frequency of occurrence of clinical and biochemical syndromes in nonalcoholic steatohepatitis
depending on the presence of CKN, %
Syndromes Groups of examined patients
NASH, n=52 NASH + CKD, n=160
Absolute data % Absolute data %
Astheno -vegetative 32 61,5 157 98,1*
Dyspeptic 31 59,6 127 79,4*
Discomfort in the right subcostal area 17 32,7 135 84,4*
Cholestatic (clinical) 9 17,3 60 37,5*
Hepatomegaly 45 86,5 160 100*
Splenomegaly 7 13,5 47 29,4*
Cytolysis 52 100,0 160 100,0
Cholestasis (biochemical) 10 19,2 69 43,1*
Mesenchymal-inflammatory 25 48,1 112 70,0*
Hepatic-cellular insufficiency 11 21,2 71 44,4*
Impairment of glucose tolerance 39 75,0 148 92,5*
Note: * - the difference is statistically significant in comparison with the indicator in the group of patients with NASH, CKD and obesity (p <0.05)
Clinical and biochemical cholestatic syndrome was established in a large proportion of patients with NASH in both groups, which was manifested by itching of the skin, bitterness in the mouth, the presence of xanthomatotic formations on the eyelids, hyperbilirubinemia due to the direct fraction of bilirubin, increased activity of Alkaline phosphatase and r-GT (Table 2) , however, in patients in the group 2, the cholestasis frequency exceeded the index in group 1 -respectively, at 2.1 (clinically) and 2.3 times (with biochemical confirmation of cholestasis markers) (p <0.05). In a small number of patients in group 1, splenomegaly was detected (13.5%), but in the patients in group 2, the frequency of splenomegaly exceeded the rate of group 1 by 2.2 times (p <0.05).
Among the biochemical syndromes, in both groups cytolytic (100.0%), cholestatic (in 21.2% of patients in group 1 and 43.1% in patients with group 2, p <0.05), mesenchymal-inflammatory syndrome (correspondingly, in 48,1% versus 70,0%, p <0,05) and Hepatocellular insufficiency syndrome (21,2% versus 44,4%, p <0,05, respectively) was noted, which exceeded the frequency of NASH biochemical syndromes in group 1 - in 1,5-2,1 times (p <0,05).
In the distribution of patients with a comorbid flow of NAS and NASH with CKD and obesity by the frequency of clinical and biochemical syndromes of NAFLD depending on the stage of CKD, the following interdependence is established (Table 3).
The incidence of astheno-vegetative syndrome in patients with NASH with CKD stage I was 1.7 times higher compared with patients with NAS with CKD stage I (p <0.05). The incidence of astheno-vegetative syndrome in patients with NASH with CKD of the II stage was 1.4 times higher than that of the patients with NAS with CKD of the II stage (p <0.05). However, the intensity and frequency of this syndrome probably increased with the growth of the stage of CKD (p <0,05) only in patients with NAS (Table 3). The frequency of dyspeptic syndrome in patients with NASH in the CKD stage I was 3.0 times higher than that of the patients with NAS and CKD stage I (p <0.05). The frequency of dyspepsia in patients with NASH with CKD II stage was 2.6 times higher compared with patients with NAS with CKD II stage (p <0,05). However, the intensity and frequency of this syndrome probably increased with the growth of the stage of CKD (p <0,05) in patients with both the NAS and NASH (Table 3).The frequency of dyspeptic syndrome in patients with NASH with CKD of the III stage significantly exceeded the rate in patients with NAS with CKD III stage in 1,7 times (p <0,05). These patterns indicate an important role of CKD in the formation of intoxication syndrome, whose intensity increases with an increase in the stage of CKD and is clinically manifested by astheno-vegetative and dyspeptic syndromes.
Table 3.
Frequency of clinical and biochemical syndromes manifestations in nonalcoholic steatosis of liver and non-alcoholic steatohepatitis in patients with obesity and CKD depending on the stage of CKD
(n,%)
Syndromes Groups of examined patients
NAS, obesity, CKD, n=110 NASH, obesity, CKD, n=160
CKD stage I, n=45 II, n=36 III, n=29 I, n=63 II, n=52 III, n=45
Astheno-vegetative 25 (55,6) 26 (72,2) 27 (93,1) 60 (95,2)* 52 (100)* 45 (100)
Dyspeptic 10 (22,2) 12 (33,3) 15 (51,7) 42 (66,7)* 45 (86,5)* 40 (88,9)*
Cholestatic (clinical) 9 (20,0) 11 (30,6) 14 (48,3) 14 (22,2) 20 (38,5) 26 (57,8)
Hepatomegaly 42 (93,3) 36 (100) 29 (100) 63 (100) 52 (100) 45 (100)
Splenomegaly 3 (6,7) 4 (11,1) 6 (20,7) 10 (15,9)* 15 (28,8)* 22 (48,9)*
Cytolysis - - - 63 (100) 52 (100) 45 (100)
Cholestasis (biochemical) 11 (24,4) 15 (41,6) 17 (58,6) 16 (25,4) 23 (44,2) 30 (66,7)*
Mesenchymal-inflammatory - - - 63 (100) 52 (100) 45 (100)
Hepatic-cellular insufficiency 1 (2,2) 3 (8,3) 4 (13,8) 16 (25,4)* 24 (46,2)* 31 (68,9)*
Impairment of glucose tolerance 33 (73,3) 35 (97,2) 29 (100) 51 (81,0)* 52 (100) 45 (100)
The incidence of clinical manifestations of cholestasis syndrome in patients with NAS and NASH increased significantly with an increase in the stage of CKD from stage I to stage III (p <0.05), indicating the role of the renal function impairment in providing liver bile homeostasis. At the same time, the biochemical cholestasis syndrome was encountered even more with an increase in the frequency of its occurrence from I to III stages of CKD in patients with NAS and NASH (p <0,05). Comorbid CKD imposes a significant imprint on the course of NAFLD with the formation of an additional component of endogenous intoxication, energy starvation, violation of the processes of formation and transport of bile micelles on the cholangiolar polyposis of the hepatocyte and the outflow of bile in the intestine physiologically. The consequence of these processes is the formation of intrahepatic cholestasis at the stage of the NAS, as well as the progress of NASH.The frequency of hepatomegaly in patients with NAS and NASH did not depend on the stage of CKD (p> 0.05). However, the splenomegaly syndrome arose directly in proportion to the growth of the comorbid CKD stage (see Table 3). The frequency of splenomegaly in patients with NASH and CKD of the I stage was 2.5 times higher than that of the patients with NAS and CKD stage I (p <0.05). The frequency of splenomegaly in patients with NASH and CKD II stage was 2.5 times higher than that of patients with NAS and CKD II stage (P <0.05).
Conclusion. Clinical course of nonalcoholic steatosis and steatohepatitis with the comorbidity with obesity and CKD is characterized by higher frequency and intensity of clinical syndromes.
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Работа поступила в редакцию 15.01.2019 года.
Рекомендована к печати на заседании редакционной коллегии после рецензирования
УДК 616.12-008.331.1-03-055
DOI http://dx.doi.org/10.5281/zenodo.2639518
Л. I. Загородня, Т. М. Ямшова ГЕНДЕРН1 ОСОБЛИВОСТ1 ПЕРЕБ1ГУ rinEPTOHI4HOÏ ХВОРОБИ
Одеський нацюнальний медичний ушверситет
Summary. Zagorodnyia L. I., Yamilova T. N. GENDER FEATURES OF
HYPERTENSIVE DISEASE COURSE. - Odessa National Medical University, e-mail: profpat@ukr.net. Objective: to study the features of the course of hypertension in men and women, as well as to identify the initial changes in kidney damage in this category of patients. Gender features during hypertension, as well as multidirectional changes in glomerular filtration between men and women were identified.
Key words: hypertension, gender, kidney, glomerular filtration rate.
Реферат. Загородняя Л. И., Ямилова Т. Н. ГЕНДЕРНЫЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНИ. Цель исследования: изучить особенности течения гипертонической болезни у мужчин и женщин, а также выявить начальные изменения поражения почек у данной категории больных. Выявлены гендерные особенности в течении гипертонической болезни, а также разнонаправленные изменения клубочковой фильтрации между мужчинами и женщинами.
Ключевые слова: гипертоническая болезнь, гендерные особенности, почки, скорость клубочковой фильтрации.
© Загородня Л. I., Ямшова Т. М.
